The present invention relates to a series of new derivatives of the compound "radicicol", which is also known by the name "monorden", and provides methods and compositions using them as well as processes for their preparation.
Radicicol (Merck Index, 11th Edition, monograph No 6163, "Monorden") was first isolated in 1953, and its structure was elucidated in 1964 by Mirrington et al. [Tetrahedron Letters, 7, 365 (1964)], who also disclosed the diacetyl derivative of radicicol. At that time, it was known to have an activity which can be broadly described as "antibiotic" (as it is described in the Merck Index), although, in fact, its activity is strictly anti-fungal. It is also known to have a relatively strong tranquilizing activity without having any effect on the central nervous system. Subsequently, it was disclosed in U.S. Pat. No. 3,428,526 that radicicol has a strong inhibitory effect in vitro on the growth of tumor cells of the mouse mastocytoma P-815. However, to date, no commercial use for the compound has been found.
We have found that radicicol itself can exert little anti-tumor activity against various types of tumor in vivo, and have also surprisingly found that certain acylated derivatives of radicicol demonstrate a superior anti-tumor activity. It is believed that the relative inactivity in vivo compared to the good activity in vitro may be a result of an instability of the compound to a component of the mammalian metabolism. We have, however, found that acylated derivatives of radicicol have greater stability in the mammalian body and can, therefore, be of practical use in the treatment of tumors.